Anterior Cingulate Cortex Modulation of the Ventral Tegmental Area in an Effort Task  Thomas W. Elston, David K. Bilkey  Cell Reports  Volume 19, Issue 11, Pages 2220-2230 (June 2017) DOI: 10.1016/j.celrep.2017.05.062 Copyright © 2017 The Authors Terms and Conditions

Cell Reports 2017 19, 2220-2230DOI: (10.1016/j.celrep.2017.05.062) Copyright © 2017 The Authors Terms and Conditions

Figure 1 Schematic of the Maze and Protocol (A) Rats initiated laps by pressing a wall-mounted touch screen. After a 2-s delay, the start box door opened, and rats ran through regions 1–9. Arrows indicate the direction of travel in the maze. The red and yellow circles indicate the position of the photobeams that controlled the doors, ensuring unidirectional travel in each trial. The mound of cereal pellets in region 9 indicates the reward zone. (B) The experiment consisted of three phases: B1 (50% barrier), phase 2 (either 0% barrier or 100% barrier), and B2 (50% barrier, identical to B1). Cell Reports 2017 19, 2220-2230DOI: (10.1016/j.celrep.2017.05.062) Copyright © 2017 The Authors Terms and Conditions

Figure 2 Electrophysiological Recording Sites (A) Plates from Paxinos and Watson (1997) indicating typical electrode placement in the ACC (AP, 2.7 mm, ML, 0.4 mm; DV, −1.8 mm from the dura), VTA (AP, −5.3 mm; ML, 1.0 mm; DV, −8.2 mm from the dura), and dCA1 (AP, −3.6 mm; ML, 2.0 mm; DV, −2.8 mm from the dura). (B) Histology indicating example electrode placement in the ACC, VTA, and dCA1. See also Figure S1. Cell Reports 2017 19, 2220-2230DOI: (10.1016/j.celrep.2017.05.062) Copyright © 2017 The Authors Terms and Conditions

Figure 3 Theta Power and Coherence Heatmapped onto Maze Positions for the ACC, VTA, and dCA1 in Flat and Barrier Trials, Respectively, for One Recording Session during B1 The barrier was located on the right side of the maze; because of the wide-field lens on our tracking camera, the animals’ trajectory over the barrier on barrier trials appears as a lateral motion. ACC, VTA, and ACC-VTA coherence data are from rat A. dCA1 power and ACC-dCA1 coherence data are from rat F. See also Figure S1. Cell Reports 2017 19, 2220-2230DOI: (10.1016/j.celrep.2017.05.062) Copyright © 2017 The Authors Terms and Conditions

Figure 4 Enhanced Theta Power and Coherence Correspond with Absence of the Barrier Shown are ACC and VTA time-resolved theta power, theta coherence, and running speed as a function of position for rat A (B1, 0%, and B2; mean ± SEM; n = 350 trials for B1, n = 150 trials for 0% barrier, and n = 150 trials for B2) and rat T (100% barrier; mean ± SEM; 150 trials for 100% barrier). In some cases, the SEM was smaller than the height of the symbol in the plot. In those instances, the error bars were not drawn. The average power and coherence between 4 and 12 Hz for each region on each lap was used. ∗p < 0.05, ∗∗p < 0.005, ∗∗∗p < 0.0005, t tests. See also Figures S1–S4. Cell Reports 2017 19, 2220-2230DOI: (10.1016/j.celrep.2017.05.062) Copyright © 2017 The Authors Terms and Conditions

Figure 5 ACC and VTA Theta and Coherence Responses to the Presence or Absence of the 30-cm Barrier in the Barrier-Containing Region of the Maze Were Consistent across Days and Conditions The data shown are from rat A. VTA (A) and ACC (B) theta power and coherence (C) were greater in trials when the barrier was present than when the barrier was absent across all days of B1 and B2 (p < 0.0005, t tests). Data are presented as mean ± SEM. In some cases, the SEM was smaller than the height of the symbol in the plot. In those instances, the error bars were not drawn. n = 50 for each session. ∗p < 0.05, ∗∗p < 0.005, ∗∗∗p < 0.0005, t tests. Cell Reports 2017 19, 2220-2230DOI: (10.1016/j.celrep.2017.05.062) Copyright © 2017 The Authors Terms and Conditions

Figure 6 ACC but Not dCA1 Theta Power Was Significantly Modulated by the Presence or Absence of a 30-cm Barrier The data are from rat F. Data are presented as mean ± SEM. In some cases, the SEM was smaller than the height of the symbol in the plot. In those instances, the error bars were not drawn. n = 350 trials for B1, n = 150 trials for 0% barrier, and n = 150 trials for B2. ∗p < 0.05, ∗∗p < 0.005, ∗∗∗p < 0.0005, t tests. See also Figures S2 and S4. Cell Reports 2017 19, 2220-2230DOI: (10.1016/j.celrep.2017.05.062) Copyright © 2017 The Authors Terms and Conditions

Figure 7 ACC-VTA and ACC-dCA1 PDC in the Barrier Region (A) ACC → VTA and VTA → ACC theta PDC in the barrier region across the three phases. (B) ACC → dCA1 and dCA1 → ACC theta PDC in the barrier region across the three phases. (C) ACC → VTA and VTA → ACC PDC in the initial region (region 2) across the three phases. (A) and (C) show data from rat B; the data in (B) are from rat G. n = 350 trials for B1, n = 150 trials for 0% and 100% barrier, and n = 150 trials for B2. Data are represented as mean ± SEM. In some cases, the SEM was smaller than the height of the symbol in the plot. In those instances, the error bars were not drawn. See also Tables S2–S6. Cell Reports 2017 19, 2220-2230DOI: (10.1016/j.celrep.2017.05.062) Copyright © 2017 The Authors Terms and Conditions